scholarly journals The Protective Effects of Isoliquiritigenin and Glycyrrhetinic Acid against Triptolide-Induced Oxidative Stress in HepG2 Cells Involve Nrf2 Activation

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Ling-Juan Cao ◽  
Huan-De Li ◽  
Miao Yan ◽  
Zhi-Hua Li ◽  
Hui Gong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepg2 Cells ◽  
Target Genes ◽  
Biological Activities ◽  
Antioxidant Response ◽  
Current Data ◽  
Glycyrrhetinic Acid ◽  
Protective Effects ◽  
Nrf2 Activation ◽  
Wide Range

Triptolide (TP), an active ingredient ofTripterygium wilfordiiHook f., possesses a wide range of biological activities. Oxidative stress likely plays a role in TP-induced hepatotoxicity. Isoliquiritigenin (ISL) and glycyrrhetinic acid (GA) are potent hepatoprotection agents. The aim of the present study was to investigate whether Nrf2 pathway is associated with the protective effects of ISL and GA against TP-induced oxidative stress or not. HepG2 cells were treated with TP (50 nM) for 24 h after pretreatment with ISL and GA (5, 10, and 20 μM) for 12 h and 24 h, respectively. The results demonstrated that TP treatment significantly increased ROS levels and decreased GSH levels. Both ISL and GA pretreatment decreased ROS and meanwhile enhanced intracellular GSH content. Additionally, TP treatment obviously decreased the protein expression of Nrf2 and its target genes including HO-1 and MRP2 except NQO1. Moreover, both ISL and GA displayed activities as inducers of Nrf2 and increased the expression of HO-1, NQO1, and MRP2. Taken together the current data confirmed that ISL and GA could activate the Nrf2 antioxidant response in HepG2 cells, increasing the expression of its target genes which may be partly associated with their protective effects in TP-induced oxidative stress.

Liraglutide Ameliorates Lipotoxicity-Induced Oxidative Stress by Activating the NRF2 Pathway in HepG2 Cells

2020 ◽  
Vol 52 (07) ◽  
pp. 532-539 ◽  
Author(s):  
Chong-gui Zhu ◽  
Ying Luo ◽  
Hao Wang ◽  
Jun-Yi Li ◽  
Jie Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Mrna Expression ◽  
Hepg2 Cells ◽  
Target Genes ◽  
Nuclear Translocation ◽  
Thiobarbituric Acid ◽  
Related Factor ◽  
Protective Effects ◽  
Alcoholic Fatty Liver

AbstractAlthough glucagon-like peptide-1 (GLP-1) analogue has been reported to suppress oxidative stress in non-alcoholic fatty liver disease (NAFLD), an effective therapeutic agent for NAFLD is currently unavailable. Therefore, in this study, we aimed to investigate the protective effects of the GLP-1 analogue liraglutide against lipotoxicity-induced oxidative stress in HepG2 cells and to elucidate the underlying mechanisms. HepG2 cells were cultured for 48 hours and treated with a free fatty acid (FFA) mixture: FFA mixture and liraglutide or FFA mixture, liraglutide, and exendin (9–39). Lipid accumulation was examined by oil red O staining. Oxidative stress was assessed by measuring the levels of intracellular reactive oxygen species using 2′,7′-dichlorofluorescein diacetate and thiobarbituric acid-reactive substances, whereas antioxidant capacity was assessed by measuring the activity of superoxide dismutase and catalase. Expression of the nuclear factor erythroid-2-related factor 2 (NRF2) gene and the genes encoding antioxidant enzymes was analyzed using quantitative RT-PCR. Cellular and nuclear NRF2 expression levels were assessed using immunofluorescence cell staining and western blotting. Liraglutide treatment reduced high fat-induced lipid formation and the levels of oxidative stress markers and increased antioxidant enzyme activity in HepG2 cells. Liraglutide treatment increased the mRNA expression of NRF2 target genes, induced NRF2 nuclear translocation, and increased nuclear NRF2 levels without altering NRF2 mRNA expression. Collectively, these results indicate that liraglutide exhibits a protective effect against lipotoxicity-induced oxidative stress, possibly via modulation of NRF2 and expression of antioxidant enzymes in liver cells.

scholarly journals Aqueous Extract of Pepino Leaves Ameliorates Palmitic Acid-Induced Hepatocellular Lipotoxicity via Inhibition of Endoplasmic Reticulum Stress and Apoptosis

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 903
Author(s):  
Jen-Ying Hsu ◽  
Hui-Hsuan Lin ◽  
Charng-Cherng Chyau ◽  
Zhi-Hong Wang ◽  
Jing-Hsien Chen
Keyword(s):  
Fatty Acid ◽  
Palmitic Acid ◽  
Er Stress ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Target Genes ◽  
Liver Lipid ◽  
Antioxidant Response ◽  
Long Chain Fatty Acid ◽  
Nrf2 Expression

Saturated fatty acid is one of the important nutrients, but contributes to lipotoxicity in the liver, causing hepatic steatosis. Aqueous pepino leaf extract (AEPL) in the previous study revealed alleviated liver lipid accumulation in metabolic syndrome mice. The study aimed to investigate the mechanism of AEPL on saturated long-chain fatty acid-induced lipotoxicity in HepG2 cells. Moreover, the phytochemical composition of AEPL was identified in the present study. HepG2 cells treated with palmitic acid (PA) were used for exploring the effect of AEPL on lipid accumulation, apoptosis, ER stress, and antioxidant response. The chemical composition of AEPL was analyzed by HPLC-ESI-MS/MS. AEPL treatment reduced PA-induced ROS production and lipid accumulation. Further molecular results revealed that AEPL restored cytochrome c in mitochondria and decreased caspase 3 activity to cease apoptosis. In addition, AEPL in PA-stressed HepG2 cells significantly reduced the ER stress and suppressed SREBP-1 activation for decreasing lipogenesis. For defending PA-induced oxidative stress, AEPL promoted Nrf2 expression and its target genes, SOD1 and GPX3, expressions. The present study suggested that AEPL protected from PA-induced lipotoxicity through reducing ER stress, increasing antioxidant ability, and inhibiting apoptosis. The efficacy of AEPL on lipotoxicity was probably concerned with kaempferol and isorhamnetin derived compounds.

scholarly journals Keap1 deletion accelerates mutant K-ras/p53-driven cholangiocarcinoma

2020 ◽  
Vol 318 (3) ◽  
pp. G419-G427 ◽  
Author(s):  
Tatsuhide Nabeshima ◽  
Shin Hamada ◽  
Keiko Taguchi ◽  
Yu Tanaka ◽  
Ryotaro Matsumoto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cancer Progression ◽  
Stress Responses ◽  
Target Genes ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Related Factor ◽  
Loss Of Function ◽  
P53 Expression ◽  
Nrf2 Activation

The activation of the Kelch-like ECH-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2) pathway contributes to cancer progression in addition to oxidative stress responses. Loss-of-function Keap1 mutations were reported to activate Nrf2, leading to cancer progression. We examined the effects of Keap1 deletion in a cholangiocarcinoma mouse model using a mutant K-ras/ p53 mouse. Introduction of the Keap1 deletion into liver-specific mutant K-ras/ p53 expression resulted in the formation of invasive cholangiocarcinoma. Comprehensive analyses of the gene expression profiles identified broad upregulation of Nrf2-target genes such as Nqo1 and Gstm1 in the Keap1-deleted mutant K-ras/ p53 expressing livers, accompanied by upregulation of cholangiocyte-related genes. Among these genes, the transcriptional factor Sox9 was highly expressed in the dysplastic bile duct. The Keap-Nrf2-Sox9 axis might serve as a novel therapeutic target for cholangiocarcinoma. NEW & NOTEWORTHY The Keap1-Nrf2 system has a wide variety of effects in addition to the oxidative stress response in cancer cells. Addition of the liver-specific Keap1 deletion to mice harboring mutant K-ras and p53 accelerated cholangiocarcinoma formation, together with the hallmarks of Nrf2 activation. This process involved the expansion of Sox9-positive cells, indicating increased differentiation toward the cholangiocyte phenotype.

scholarly journals Neurological Alterations and Testicular Damages in Aging Induced by D-Galactose and Neuro and Testicular Protective Effects of Combinations of Chitosan Nanoparticles, Resveratrol and Quercetin in Male Mice

Coatings ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 435
Author(s):  
Reham Z. Hamza ◽  
Mohammad S. Al-Harbi ◽  
Munirah A. Al-Hazaa
Keyword(s):  
Oxidative Stress ◽  
Chitosan Nanoparticles ◽  
Oxidative Stress Marker ◽  
Control Group ◽  
Antioxidant Enzyme Activities ◽  
Enzymatic Antioxidants ◽  
Protective Effects ◽  
Biochemical Alterations ◽  
Wide Range ◽  
Neurological Alterations

Aging is a neurological disease that is afforded by incidence of oxidative stress. Chitosan has received global interests due to its wide medical uses. Quercetin (Q) is a bioflavonoid and widely distributed in vegetables and fruits. Resveratrol is considered as a potent antioxidant and is a component of a wide range of foods. The using of either chitosan nanopartciles (CH-NPs), querectin (Q), and resveratrol (RV) to reduce the oxidative stress and biochemical alterations on brain and testicular tissues induced by D-galactose (DG) (100 mg/Kg) were the aim of the present study. This study investigated the probable protective effects of CH-NPs in two doses (140,280 mg/Kg), Q (20 mg/Kg) and RV (20 mg/Kg), against DG induced aging and neurological alterations. Brain antioxidant capacity as malonaldehyde (MDA), catalase (CAT), and glutathione reductase (GRx), as well as histopathological damages of the brain and testicular tissues were measured. The DG treated group had significantly elevated the oxidative stress markers by 96% and 91.4% in brain and testicular tissues respectively and lower significantly the antioxidant enzyme activities of both brain and testicular tissues than those of the control group by 86.95%, 69.27%, 83.07%, and 69.43%. Groups of DG that treated with a combination of CH-NPs in two doses, Q and RV, the levels of oxidative stress marker declined significantly by 68.70%, 76.64% in brain tissues and by 74.07% and 76.61% in testicular tissues, and the enzymatic antioxidants increased significantly by 75.55%, 79.24%, 62.32%, and 61.97% as compared to the DG group. The present results indicate that CH-NPs, Q, and RV have protective effects against DG-induced brain and testis tissue damage at the biochemical and histopathological levels. Mechanisms of this protective effect of used compounds against neurological and testicular toxicity may be due to the enhanced brain and testis antioxidant capacities.

The protective effects of carvacrol and thymol against paracetamol–induced toxicity on human hepatocellular carcinoma cell lines (HepG2)

2016 ◽  
Vol 35 (12) ◽  
pp. 1252-1263 ◽  
Author(s):  
SS Palabiyik ◽  
E Karakus ◽  
Z Halici ◽  
E Cadirci ◽  
Y Bayir ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Hepg2 Cells ◽  
Folk Medicine ◽  
Hepatoprotective Activity ◽  
High Dose ◽  
Protective Effects ◽  
And Oxidative Stress ◽  
Pro Inflammatory Cytokines

Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 µM) were tested on cultured HepG2 cells. N-Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol.

Fumonisin B1-induced oxidative stress triggers Nrf2-mediated antioxidant response in human hepatocellular carcinoma (HepG2) cells

2018 ◽  
Vol 35 (1) ◽  
pp. 99-109 ◽  
Author(s):  
Thilona Arumugam ◽  
Yashodani Pillay ◽  
Terisha Ghazi ◽  
Savania Nagiah ◽  
Naeem Sheik Abdul ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepatocellular Carcinoma ◽  
Hepg2 Cells ◽  
Fumonisin B1 ◽  
Antioxidant Response ◽  
Human Hepatocellular Carcinoma

scholarly journals PICH, an ATP-dependent chromatin remodeling protein, transcriptionally co-regulates oxidative stress response.

2021 ◽  
Author(s):  
Anindita Dutta ◽  
Apurba Das ◽  
Deep Bisht ◽  
Vijendra Arya ◽  
Rohini Muthuswami
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Stress Response ◽  
Chromatin Remodeling ◽  
Dna Sequences ◽  
Target Genes ◽  
Antioxidant Response ◽  
Oxidative Stress Response ◽  
Antioxidant Genes

Cells respond to oxidative stress by elevating the levels of antioxidants, signaling, and transcriptional regulation often implemented by chromatin remodeling proteins.  The study presented in this paper shows that the expression of PICH, an ATP-dependent chromatin remodeler, is upregulated during oxidative stress in HeLa cells. We also show that PICH regulates the expression of Nrf2, a transcription factor regulating antioxidant response, both in the absence and presence of oxidative stress. In turn, Nrf2 regulates the expression of PICH in the presence of oxidative stress. Both PICH and Nrf2 together regulate the expression of antioxidant genes and this transcriptional regulation is dependent on the ATPase activity of PICH. In addition, H3K27ac modification also plays a role in activating transcription in the presence of oxidative stress. Co-immunoprecipitation experiments show that PICH and Nrf2 interact with H3K27ac in the presence of oxidative stress. Mechanistically, PICH recognizes ARE sequences present on its target genes and introduces a conformational change to the DNA sequences leading us to hypothesize that PICH regulates transcription by remodeling DNA. PICH ablation leads to reduced expression of Nrf2 and impaired antioxidant response leading to increased ROS content, thus, showing PICH is essential for the cell to respond to oxidative stress.

scholarly journals Propolis Protective Effects Against Doxorubicin-Induced Multi-Organ Toxicity via Suppression of Oxidative Stress, Inflammation, Apoptosis, and Histopathological Alterations in Female Albino Rats

2021 ◽  
Vol 12 (2) ◽  
pp. 1762-1777
Keyword(s):  
Oxidative Stress ◽  
Large Scale ◽  
Protective Efficacy ◽  
Biological Activities ◽  
Female Rats ◽  
Control Group ◽  
Albino Rats ◽  
Protective Agent ◽  
Protective Effects ◽  
Treatment Protocols

Doxorubicin (DOX) is effective chemotherapy in several malignancies, but large-scale toxicities limit its clinical usefulness. Propolis has been reported to exhibit a broad spectrum of biological activities. We aim to assess the protective efficacy of propolis against DOX-induced multi-toxicity in female rats. Forty female rats were divided into four groups: control group; Group (P) were administrated oral propolis (100 mg/kg once daily for 28 days); Group (P+DOX) were injected with a single intraperitoneal dose of DOX (20 mg/kg i.p at 24th day after the propolis administration) and group (DOX) were injected with doxorubicin only. Estimation of cardiac, renal and hepatic injury markers, apoptosis and pro-inflammatory cytokines were done using sera. Also, liver and heart tissue samples were collected to determine GSH and MDA as oxidative stress markers. In addition to histopathological and immunohistochemical examination of Cytochrome-C and Connexin43 on lysed myocardium, liver, kidney and lung tissues. Doxorubicin toxicity caused marked deteriorations of measured parameters through the different mechanisms in different body organs. However, pre-treatment with propolis significantly ameliorated these alterations. Thus propolis can ameliorate the DOX-induced experimental multi-toxicity as cardiomyopathy, hepatotoxicity, nephritis and pneumonia. Thus, it could be a promising protective agent in DOX treatment protocols.

scholarly journals Protective Effects of Aqueous Extract of Mentha suaveolens against Oxidative Stress-Induced Damages in Human Keratinocyte HaCaT Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
HansongI Lee ◽  
Miji Yeom ◽  
Seoungwoo Shin ◽  
Kyungeun Jeon ◽  
Deokhoon Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Phase Ii ◽  
Aqueous Extract ◽  
Biological Activities ◽  
Ros Generation ◽  
Related Factor ◽  
Hacat Cells ◽  
Human Keratinocyte ◽  
Wide Range ◽  
Phase Ii Enzyme

Mentha suaveolens is an aromatic herb that has a wide range of biological activities, including antimicrobial, antifungal, anti-inflammatory, and hepatoprotective properties. Although there are a few reports on the antioxidant property of M. suaveolens, its cytoprotective activity against oxidative stress has not been reported yet. The objective of this study was to determine the protective activity of M. suaveolens aqueous extract (MSAE) against hydrogen peroxide- (H2O2-) induced oxidative stress and apoptosis in human keratinocyte HaCaT cells. MSAE pretreatment decreased H2O2-induced cytotoxicity and suppressed H2O2-induced intracellular ROS generation. Furthermore, MSAE suppressed expression levels of H2O2-induced apoptotic genes such as cleaved caspase-3, caspase-9, and cleaved poly (ADP-ribose) polymerase (PARP). Pretreatment with MSAE induced expression of phase II enzyme such as HO-1 through translocation of NF-E2-related factor (Nrf2) upon H2O2 exposure. These results revealed that the cytoprotective effect of MSAE against oxidative stress-induced cell death was associated with activation of Nrf2-mediated phase II enzyme expression.

Epimedium koreanum Ameliorates Oxidative Stress-Mediated Liver Injury by Activating Nuclear Factor Erythroid 2-Related Factor 2

2018 ◽  
Vol 46 (02) ◽  
pp. 469-488 ◽  
Author(s):  
Ji Yun Jung ◽  
Sang Mi Park ◽  
Hae Li Ko ◽  
Jong Rok Lee ◽  
Chung A Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Hepg2 Cells ◽  
Liver Diseases ◽  
Caspase 3 ◽  
Glutathione Depletion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Activation ◽  
Anti Oxidant

Oxidative stress induced by reactive oxygen species is the main cause of various liver diseases. This study investigated the hepatoprotective effect of Epimedium koreanum Nakai water extract (EKE) against arachidonic acid (AA)[Formula: see text][Formula: see text][Formula: see text]iron-mediated cytotoxicity in HepG2 cells and carbon tetrachloride (CCl4-)-mediated acute liver injury in mice. Pretreatment with EKE (30 and 100[Formula: see text][Formula: see text]g/mL) significantly inhibited AA[Formula: see text][Formula: see text][Formula: see text]iron-mediated cytotoxicity in HepG2 cells by preventing changes in the expression of cleaved caspase-3 and poly(ADP-ribose) polymerase. EKE attenuated hydrogen peroxide production, glutathione depletion, and mitochondrial membrane dysfunction. EKE also increased the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), transactivated anti-oxidant response element harboring luciferase activity, and induced the expression of anti-oxidant genes. Furthermore, the cytoprotective effect of EKE against AA[Formula: see text][Formula: see text][Formula: see text]iron was blocked in Nrf2 knockout cells. Ultra-performance liquid chromatography analysis showed that EKE contained icariin, icaritin, and quercetin; icaritin and quercetin were both found to protect HepG2 cells from AA[Formula: see text][Formula: see text][Formula: see text]iron via Nrf2 activation. In a CCl4-induced mouse model of liver injury, pretreatment with EKE (300[Formula: see text]mg/kg) for four consecutive days ameliorated CCl4-mediated increases in serum aspartate aminotransferase activity, histological activity index, hepatic parenchyma degeneration, and inflammatory cell infiltration. EKE also decreased the number of nitrotyrosine-, 4-hydroxynonenal-, cleaved caspase-3-, and cleaved poly(ADP-ribose) polymerase-positive cells in hepatic tissues. These results suggest EKE is a promising candidate for the prevention or treatment of oxidative stress-related liver diseases via Nrf2 activation.

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